Rotor’s syndrome is an Autosomal recessive inherited disorder characterized by a deject in biliary excretion leading to conjugated hyperbilirubinemia:

Indirect hyperbilirubinemia

Direct hyperbilirubinemia

A. Hemolytic disorders

A. Inherited conditions

1. Inherited

1. Dubin-Johnson syndrome

a. Sperocyteosis, elliptocytosis

2. Rotor’s syndrome

Glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies

b. Sickle cell anemia

2. Acquired _

a. Microangiopathic hemolytic anemias

b. Paraoxysmal nocturnal hemoglobinuria

c. Immune hemolysis

B. Ineffective erythropoesis

1. Cobalamin, folate, thalassemia, and severe iron deficiencies

C. Drugs

1. Rifampicin, probenbecid, ribavirin

D. Inherited conditions

1. Crigler-Najjar types I and II

2. Glibert’s syndrome

Q. 9

A patient presents with unconjugated hyperbilirubinemia and presence of urobilinogen in urine. Which amongst the following is the least likely diagnosis:

A

Hemolytic jaundice

B

Crigler Najjar syndrome

C

Gilbert’s syndrome

D

Dubin Johnson syndrome

Q. 9

A patient presents with unconjugated hyperbilirubinemia and presence of urobilinogen in urine. Which amongst the following is the least likely diagnosis:

A

Hemolytic jaundice

B

Crigler Najjar syndrome

C

Gilbert’s syndrome

D

Dubin Johnson syndrome

Ans.

D

Explanation:

Answer is D (Dubin Johnson Syndrome)

Dubin Johnson syndrome is associated with conjugated hyperbilirubinemia & not unconjugated hjperbilirubinemia. Dubin Johnson Syndrome results from a hereditary defect in excretion of conjugated bilirubin across the canalicular membrane and leads to conjugated hyperbilirubinemia.

Dubin Johnson syndrome is an inherited disorder charachterized by defective excretion of conjugated bilirubin from hepatocytes into biliary canaliculi. It thus presents with a clinical picture similar to obstructive jaundice with conjugated hyperbilirubinemia and absence of urobilinogen in urine.

Hemolytic Anemia typically presents with unconjugated hyperbilirubinemia and elevated urinary urobilinogens. Gilberts syndrome and Cri2ler Najjar syndrome also present with unconjugated hyperbilirubinemia. Urinary Urobilinogens are however not elevated in these conditions. Urobilinogen may never the less be present in urine (N or in these conditions

Q. 10

Conjugated hyperbilirubinemia is seen in all EX­CEPT:

March 2013

A

Dubin Johnson syndrome

B

Rotor syndrome

C

Gilbert syndrome

D

None of the above

Q. 10

Conjugated hyperbilirubinemia is seen in all EX­CEPT:

March 2013

A

Dubin Johnson syndrome

B

Rotor syndrome

C

Gilbert syndrome

D

None of the above

Ans.

C

Explanation:

Ans. C i.e. Gilbert syndrome

Gilbert syndrome presents with unconjugated hyperbilirubinemia

Q. 11

Unconjugated hyperbilirubinemia is seen in all of the following except:

March 2010

A

Crigler Najjar Syndrome

B

Physiological jaundice

C

Dubin-Johnson syndrome

D

Gilbert syndrome

Q. 11

Unconjugated hyperbilirubinemia is seen in all of the following except:

March 2010

A

Crigler Najjar Syndrome

B

Physiological jaundice

C

Dubin-Johnson syndrome

D

Gilbert syndrome

Ans.

C

Explanation:

Ans. C: Dubin-Johnson Syndrome

Dubin-Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin without elevation of liver enzymes (ALT, AST).

This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile.

The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile.

The brain is a rich source of glutamine synthase and predominantly detoxifies ammonia by synthesis of glutamate.

Q. 11

Which amino acid binds with NH4+ covalently and makes it non-toxic for transportation-

A

Serine

B

Aspartate

C

Glutamate

D

Histidine

Q. 11

Which amino acid binds with NH4+ covalently and makes it non-toxic for transportation-

A

Serine

B

Aspartate

C

Glutamate

D

Histidine

Ans.

C

Explanation:

Q. 12

Co factors for glutamate dehydrogenase-

A

NAD

B

FADH2

C

FMN

D

FAD

Q. 12

Co factors for glutamate dehydrogenase-

A

NAD

B

FADH2

C

FMN

D

FAD

Ans.

A

Explanation:

Hepatic L- glutamate dehydrogenase can use either NAD+ or NADP+.

Q. 13

Increased alanine during prolonged fasting represents-

A

Increased breakdown of muscle proteins

B

Impaired renal function

C

Decreased utilization of amino acid from Glucogenesis

D

Leakage of amino acids from cells due to plasma membrane leakage

Q. 13

Increased alanine during prolonged fasting represents-

A

Increased breakdown of muscle proteins

B

Impaired renal function

C

Decreased utilization of amino acid from Glucogenesis

D

Leakage of amino acids from cells due to plasma membrane leakage

Ans.

A

Explanation:

During prolonged fasting there is increased gluconeogenesis. Alanine is provided by the muscle is one of the substrates for gluconeogenesis and is called Glucose Alanine cycle.

So plasma level of alanine increases in prolonged starvation.

Q. 14

Amino acid absorption is by-

A

Facilitated transport

B

Passive transport

C

Pinocytosis

D

Active transport

Q. 14

Amino acid absorption is by-

A

Facilitated transport

B

Passive transport

C

Pinocytosis

D

Active transport

Ans.

D

Explanation:

Free amino acids are absorbed across the intestinal mucosa by sodium-dependent active transport. There are several different amino acid transporters, with specificity for the nature of the amino acid side-chain. Transporters of Amino Acids.

For Neutral Amino Acids

For Basic Amino acids and Cysteine

For Imino Acids and Glycine

For Acidic Amino Acids

For Beta Amino Acids (Beta Alanine)

Meisters Cycle

For absorption of Neutral Amino acids from Intestines, Kidney tubules and brain.

The main role is played by Glutathione. (GSH)

For transport of 1 amino acid and regeneration of GSH 3 ATPs are required.

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citric acid cycle

All of the following vitamins are required in citric acid cycle, EXCEPT:

A

Riboflavin

B

Niacin

C

Thiamin

D

Ascorbic acid

Q. 1

All of the following vitamins are required in citric acid cycle, EXCEPT:

A

Riboflavin

B

Niacin

C

Thiamin

D

Ascorbic acid

Ans.

D

Explanation:

Four of the B vitamins are essential in the citric acid cycle and hence energy-yielding metabolism: (1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor for succinate dehydrogenase; (2) niacin, in the form of nicotinamide adenine dinucleotide (NAD), the electron acceptor for isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase; (3) thiamin (vitamin B1), as thiamin diphosphate, the coenzyme for decarboxylation in the α-ketoglutarate dehydrogenase reaction; and (4) pantothenic acid, as part of coenzyme A, the cofactor attached to “active” carboxylic acid residues such as acetyl-CoA and succinyl-CoA

Ref: Harper 28th edition, chapter 17

Q. 2

The citric acid cycle is inhibited by which of the following?

A

Fluoroacetate

B

Fluorouracil

C

Arsenic

D

Aerobic conditions

Q. 2

The citric acid cycle is inhibited by which of the following?

A

Fluoroacetate

B

Fluorouracil

C

Arsenic

D

Aerobic conditions

Ans.

A

Explanation:

Fluoroacetate can be converted to fluorocitrate, which is an inhibitor of aconitase. Arsenic is not a direct inhibitor, butarsenite is an inhibitor of lipoic acid–containing enzymes such as α-ketoglutarate dehydrogenase.Malonate, not malic acid, is an inhibitor of succinate dehydrogenase. The citric acid cycle requires oxygen and would be inhibited by anaerobic, not aerobic, conditions.Fluorouracil is a suicide inhibitor of thymidylate synthase and blocks deoxythymidylate synthesis.

Myoglobin

Is characterized by the sigmoid and multiple hyperbolic saturation curve

D

Is characterized by the hyperbolic saturation curve

Q. 1

Binding of oxygen to myoglobin:

A

Is characterized by the sigmoidal saturation curve

B

Occurs at multiple sites

C

Is characterized by the sigmoid and multiple hyperbolic saturation curve

D

Is characterized by the hyperbolic saturation curve

Ans.

D

Explanation:

Myoglobin molecule contains a single O2 binding site and thus the saturation process is characterized by a simple hyperbolic curve, in contrast to hemoglobin, sigmoid saturation curve of which shows positive cooperativity of multiple oxygen binding sites.

The oxygen dissociation curve of myoglobin & hemoglobin is different due to‑

A

Hb can bind to 2 oxygen molecules

B

Cooperative binding in Hb

C

Myogloobin has little oxygen affinity

D

Hemoglobin follows a hyperbolic curve

Q. 3

The oxygen dissociation curve of myoglobin & hemoglobin is different due to‑

A

Hb can bind to 2 oxygen molecules

B

Cooperative binding in Hb

C

Myogloobin has little oxygen affinity

D

Hemoglobin follows a hyperbolic curve

Ans.

B

Explanation:

Ans. is `b’ i.e., Cooperative binding in Hb

Cooperative binding is responsible for sigmoid shape of the oxygen-hemoglobin dissociation curve.

As myoglobin is monomeric (consists of one polypeptide chain only), it can bind only one molecule of oxygen and for the same reason myoglobin cannot show the phenomenon of cooperative binding. Hence, the oxygen‑myoglobin dissociation curve is hyperbola as compared to sigmoid shape of Hb-O2 curve.

Hemoglobin – O2binding

Each molecule of hemoglobin can combine with upto four molecules of oxygen. Combination with the first molecule alters the conformation of the hemoglobin molecule in such a way as to facilitate combination with the next oxygen molecule. In light of this, if we look at the curve, as the PO2 starts rising from 0 mm Hg upwards, initially all hemoglobin molecules in blood starts combining with their first oxygen molecule. This is the most difficult molecule to combine with. Hence saturation rises only slowly with initial rise in PO2. As PO2 rises further, hemoglobin molecules combine with their second, third and fourth molecules, which are progressively easier to combine with. Hence saturation rises steeply between PO2 of 15 mm Hg and 40 mm Hg. When PO2 rises still further, oxygen finds most of the hemoglobin molecules carrying four molecules of oxygen each. Since no molecules of hemoglobin can carry more than four molecules of oxygen, there is not much scope for more O2 combining with hemoglobin. Hence the curve becomes almost flat again beyond the PO2 of 60 mm Hg.

Thus, the primary reason for the sigmoid shape of the oxygen-hemoglobin dissociation curve is that out of the four molecules of oxygen that can combine with a hemoglobin molecules, the first combines with the greatest difficulty and binding of an oxygen molecules increases affinity to next O2 molecule. This phenomenon is termed as cooperative binding or cooperativity, i.e., a molecule of O2 binds to a hemoglobin tetramer more readily if other O2 molecules are already bound.

Myoglobin O2binding

Myoglobin is present in higher concentration in red (slow) muscle fibers. Myoglobin has greater affinity for oxygen than hemoglobin and its P50 is only 5 mm Hg (as compared to PO2 of hemoglobin which is about 26 mm Hg). Therefore, myoglobin-oxygen dissociation curve is shifted far to the left than Hb-O2 dissociation curve. It has shape of hyperbola as compared to sigmoid shape of Hb-O2 curve because it binds 1 molecule of O2 per mole (in comparison to Hb which binds 4 molecules of O2 per mole). The role of myoglobin is to bind O2 at very low PO2 and release them at even lower PO2, for example in exercising muscles where PO2 close to zero.

Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell.

The two primary sites for insulin clearance are the liver and the kidney.

The liver clears most insulin during first-pass transit, whereas the kidney clears most of the insulin in systemic circulation.

Degradation normally involves endocytosis of the insulin-receptor complex, followed by the action of insulin-degrading enzyme.

An insulin molecule produced endogenously by the pancreatic beta cells is estimated to be degraded within about one hour after its initial release into circulation (insulin half-life – 4-6 minutes)

Q. 2

Crystallization and storage of insulin requires ‑

A

Mn++

B

Zn++

C

Cu++

D

Ca++

Q. 2

Crystallization and storage of insulin requires ‑

A

Mn++

B

Zn++

C

Cu++

D

Ca++

Ans.

B

Explanation:

Ans. is `b’ i.e., Zn++

Zinc ions are essential for the formation of hexameric insulin and hormone crystallization.

Following the synthesis of proinsulin, zinc promotes the formation of proinsulin hexamers and increases its solubility before conversion to insulin.

Proinsulin binds 30 zinc ions, of which 2 to 4 are coordinated within the molecule. These zinc ions appear to be important for the solubility of proinsulin hexamers.

With the removal of C-peptide from each proinsulin monomers, the resulting insulin increases its coordination of zinc to up to six ions per hexamer, which decreases its solubility and increases its crystallization within the secretory vesicle.

The insulin, stored as crystalline hexamer, is resistant from proteolytic attack within the vesicle.

Upon release of insulin into the bloodsteam, zinc is also released and the insulin becomes soluble in the blood.

Most Severe Cases: In the most severe forms of the hyperammonemic disorders, the infants are asymptomatic at birth and during the first day or two of life, after which they refuse their feedings, vomit, and rapidly become inactive and lethargic, soon lapsing into an irreversible coma. Profuse sweating, focal or generalized seizures, rigidity with opisthotonos, hypothermia, and hyperventilation have been observed in the course of the illness.

These symptoms constitute a medical emergency, but even with measures to reduce serum ammonia, the disease is usually fatal.

Aerobic glycolysis is a process of splitting of glucose into two molecules of pyruvate with the synthesis of ATP. Net ATP formed in aerobic glycolysis is 8.

Glycolysis: is the process by which glucose or other hexoses are converted into the three-carbon compound pyruvate. All the reactions takes place in cytoplasm.

Aerobic glycolysis: is a process of splitting of glucose into two molecules of pyruvate with the synthesis of ATP.

Anaerobic Glycolysis: glycolysis is the only process in which ATP is generated anaerobically. This is of importance because RBC which does not have a mitochondria is wholly dependant on the anaerobic energy production. The byproduct of anaerobic glycolysis is lactate.

Glycolytic pathway: occurs in cytoplasm consists of 10 steps. The first five steps result in one molecule of glucose is converted to 2 glyceraldehyde-3-phosphate molecules at the expense of two molecules of ATPs. The second five steps results in the production of 2 ATP molecules per one molecule of glucose.

Which of the following statements about anaerobic glycolysis is INCORRECT?

A

Anaerobic glycolysis yields two molecules of lactate and two molecules of ATP

B

There are two oxidation-reduction steps in the anaerobic glycolysis.

C

The lactated formed in the muscles in the condition of an oxygen deficit can be recycled through the Cori cycle.

D

The extraction of energy from the molecule of glucose in the anaerobic glycolysis happens due to the net change in the oxidation state of carbon

Q. 6

Which of the following statements about anaerobic glycolysis is INCORRECT?

A

Anaerobic glycolysis yields two molecules of lactate and two molecules of ATP

B

There are two oxidation-reduction steps in the anaerobic glycolysis.

C

The lactated formed in the muscles in the condition of an oxygen deficit can be recycled through the Cori cycle.

D

The extraction of energy from the molecule of glucose in the anaerobic glycolysis happens due to the net change in the oxidation state of carbon

Ans.

D

Explanation:

Although there are two oxidation-reduction steps is the anaerobic glycolysis, and the energy for the synthesis of two ATP molecules is released, there is no net change in the oxidation state of carbon. The first oxidative reaction is catalyzed by glyceraldehyde-3-phosphate dehydrogenase to yield NADH. Later, NADH is spent for the reduction of pyruvate to the lactate which is catalyzed by lactate dehydrogenase. The ratio between C, H, and O atoms is the same for both glucose, C6H12O6 and lactic acid C3H6O3.

In virtually all cells of the body, glycolysis is the primary pathway for carbohydrate catabolism.

During glycolysis, glucose undergoes oxidation to form pyruvate, NADH, and ATP. The initial reaction of glycolysis involves phosphorylation of glucose to glucose-6-phosphate via the enzyme hexokinase (glucokinase in liver).

The first committed step involves the phosphorylation of fructose-6-phosphate to fructose-1,6-diphosphate by phosphofructokinase (PFK). The reactions catalyzed by hexokinase and PFK are two of three irreversible reactions occurring in glycolysis.

The other irreversible reaction involves pyruvate kinase. In terms of the energetics of the reactants and products, it is important to remember that every intermediate in this pathway between glucose and pyruvate contains phosphate.

Within the RBC, hypoxia stimulates glycolysis by which of the following regulating pathways?

A

Hypoxia stimulates pyruvate dehydrogenase by increased 2,3 DPG

B

Hypoxia inhibits hexokinase

C

Hypoxia stimulates release of all glycolytic enzymes from band 3 on RBC membrane

D

Activation of the regulatory enzymes by high PH

Q. 8

Within the RBC, hypoxia stimulates glycolysis by which of the following regulating pathways?

A

Hypoxia stimulates pyruvate dehydrogenase by increased 2,3 DPG

B

Hypoxia inhibits hexokinase

C

Hypoxia stimulates release of all glycolytic enzymes from band 3 on RBC membrane

D

Activation of the regulatory enzymes by high PH

Ans.

C

Explanation:

During Hypoxia, the glycolytic enzymes that bind in the same region of band 3 of Hb are released from the membrane resulting in an increased rate of glycolysis. Increased glycolysis increases ATP production and the hypoxic release of ATP.

Glycolysis is the metabolic pathway that involves 10 enzyme mediated steps. It occur in which of the following cell organelle?

A

Cytosol

B

Mitochondria

C

Nucleus

D

Lysosome

Q. 10

Glycolysis is the metabolic pathway that involves 10 enzyme mediated steps. It occur in which of the following cell organelle?

A

Cytosol

B

Mitochondria

C

Nucleus

D

Lysosome

Ans.

A

Explanation:

Glycolysis, the major pathway for glucose metabolism, occurs in the cytosol of all cells. Glycolysis is both the principal route for glucose metabolism and also the main pathway for the metabolism of fructose, galactose, and other dietary carbohydrates.

Although glucose 6-phosphate is common to both pathways, the pentose phosphate pathway is markedly different from glycolysis. Oxidation utilizes NADP rather than NAD, and CO2, which is not produced in glycolysis, is a characteristic product. No ATP is generated in the pentose phosphate pathway, whereas it is a major product of glycolysis

Ref: Harper 28th edition, chapter 21.

Q. 13

Which of the following is an energy-requiring step of glycolysis?

A

Pyruvate carboxylase

B

Phosphoenolpyruvate carboxykinase

C

Phosphoglycerate kinase

D

Hexokinase

Q. 13

Which of the following is an energy-requiring step of glycolysis?

A

Pyruvate carboxylase

B

Phosphoenolpyruvate carboxykinase

C

Phosphoglycerate kinase

D

Hexokinase

Ans.

D

Explanation:

Hexokinase catalyzes the conversion of glucose to glucose-6-phosphate in the energy-requiring first step of glycolysis. ATP is also required in the conversion of fructose-6-phosphate to fructose 1,6-bisphosphate by PFK. ATP is generated in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate by phosphoglycerate kinase and in the conversion of phosphoenolpyruvate to pyruvate by PK. Both phosphoenolpyruvate carboxykinase and pyruvate carboxylase are energy-requiring reactions except that these occur in the gluconeogenesis pathway.

Glycolysis is the metabolic pathway that breaks down (catabolism) hexose (six-carbon) monosaccharides such as glucose, fructose, and galactose into two molecules of pyruvate, two molecules of ATP, two molecules of NADH, two water (H2O) molecules, and two hydrogen ions (H+).

The activation as well as the quantities of certain key enzymes of glycolysis, namely glucokinase (NOT hexokinase), phosphofructokinase and pyruvate kinase are increased by insulin.

Q. 24

Key glycolytic enzymes in glycolysis are all except:

A

Phosphofructokinase

B

Hexokinase

C

Pyruvate kinase

D

Glucose-1, 6, diphosphatase

Q. 24

Key glycolytic enzymes in glycolysis are all except:

A

Phosphofructokinase

B

Hexokinase

C

Pyruvate kinase

D

Glucose-1, 6, diphosphatase

Ans.

D

Explanation:

Glycolysis/Embden-Meyerhof pathway is the sequence of reactions that converts glucose into pyruvate with the concomitant production of a relatively small amount of adenosine triphosphate (ATP)

It is the initial process of most carbohydrate catabolism, and it serves three principal functions:

Generation of high-energy molecules (ATP and NADH) as cellular energy sources as part of aerobic respiration and anaerobic respiration.

Production of pyruvate for the citric acid cycle as part of aerobic respiration

Production of a variety of six- and three-carbon intermediate compounds, which may be removed at various steps in the process for other cellular purposes

In eukaryotes and prokaryotes, glycolysis takes place within the cytosol of the cell.

Q. 25

What is the end product of anearobic glycolysis?

A

Pyruvate

B

Lactate

C

Fats

D

Cholesterol

Q. 25

What is the end product of anearobic glycolysis?

A

Pyruvate

B

Lactate

C

Fats

D

Cholesterol

Ans.

B

Explanation:

Q. 26

Which is not a common enzyme for glycolysis and gluconeogenesis?

A

Aldolase

B

Glucose-6-phosphatase

C

Phosphoglycerate mutase

D

Phosphoglycerate kinase

Q. 26

Which is not a common enzyme for glycolysis and gluconeogenesis?

A

Aldolase

B

Glucose-6-phosphatase

C

Phosphoglycerate mutase

D

Phosphoglycerate kinase

Ans.

B

Explanation:

Seven of the reactions of glycolysis are reversible and are used in the synthesis of glucose by gluconeogenesis.

Thus, seven enzymes are common to both glycolysis and gluconeogenesis :

(i) Phosphohexose isomerase;

(ii) Aldolase;

(iii) Phosphotriose isomerase,

(iv) Glyceraldehyde 3-phosphate dehydrogenase;

(v) Phosphoglycerate kinase;

(vi) Phosphoglycerate mutase;

(vii) Enolase.

Three reactions of glycolysis are irreversible which are circumvented in gluconeogenesis by four reactions. So, enzymes at these steps are different in glycolysis and gluconeogenesis.

Q. 27

Number of ATP produced by RBC when Glycolysis occurs through Rapoport Leubering pathway

A

1

B

2

C

3

D

4

Q. 27

Number of ATP produced by RBC when Glycolysis occurs through Rapoport Leubering pathway

A

1

B

2

C

3

D

4

Ans.

A

Explanation:

Usually 2 ATP molecules are formed in glycolysis by substrate level phosphorylation.

Q. 28

Which of the following enzyme does not catalyzes irreversible step in glycolysis ‑

A

Hexokinase

B

Phosphoglycerate kinase

C

Pyruvate kinase

D

Phosphofructokinase

Q. 28

Which of the following enzyme does not catalyzes irreversible step in glycolysis ‑

A

Hexokinase

B

Phosphoglycerate kinase

C

Pyruvate kinase

D

Phosphofructokinase

Ans.

B

Explanation:

Ans. is ‘b’ i.e., Phosphoglycorate kinase

Glycolysis is regulated at 3 steps which are irreversible.

These reactions are catalyzed by following key enzymes :‑

1) Hexokinase and glucokinase

2) Phosphofructokinase – I

3) Pyruvate kinase.

Q. 29

Number of ATP molecules and NADH formed in each cycle of glycolysis ‑

A

4 ATP, 2 NADH

B

2 ATP, 2 NADH

C

4 ATP, 4 NADH

D

2 ATP, 4 NADH

Q. 29

Number of ATP molecules and NADH formed in each cycle of glycolysis ‑

A

4 ATP, 2 NADH

B

2 ATP, 2 NADH

C

4 ATP, 4 NADH

D

2 ATP, 4 NADH

Ans.

A

Explanation:

Ans. is ‘a’ i.e., 4 ATP, 2 NADH

Enegetics of glvcolysis

During glycolysis 2 ATP are utilized and 4 ATP are produced at substrate level. 2 reducing equalents NADH’ are produced and reoxidized by electron transport chain, to generata 5 ATP molecules (2.5 ATP per NADH’ molecule). Thus total 9 ATP molecules are produced and 2 are utilized, i.e., There is net gain of 7 ATP molecules in aerobic glycolysis.

In anaerobic conditions, the reoxidation of NADH by electron transport chain is prevented and NADH gets reoxidized by conversion of pyruvate to lactate by lactate dehydrogenase. Thus, in anaerobic glycolysis only 4 ATP are produced at substrate level. Therefore, there is net gain of 2 ATP molecules in anaerobic glycolysis.

Note : – Previous calculations were made assuming that NADH produces 3 ATPs and FADH2 generates 2 ATPs. This will amount to a net generation of 8ATPs per glucose molecule during glycolysis. Recent experiments show that these old values are overestimates and NADH produces 2.5 ATPs and FADH2 produces 1.5 ATPs. Thus, net generation is only 7ATPs during glycolysis.

Glycolysis is regulated at 3 steps which are irreversible. These reactions are catalyzed by following key enzymes : (1) Hexokinase and glucokinase, (2) Phosphofructokinase I, and (3) Pyruvate kinase.

Hexokinase and glucokinase

These enzymes catalyze the first step of glycolysis, i.e., Glucose —> Glucose-6-phosphate. Glucokinase is found in liver, Whereas hexokinase is found in all tissues. Kinetic properties of these two are different.

Hexokinase has low Km, i.e., high affinity for glucose, low Vmax, and is subjected to feedback inhibition by the reaction product, glucose-6-phosphate. Hexokinase is found in most of the tissue except liver and comes into play when blood glucose is low. It is not affected by feeding or insulin. Hexokinase is not specific for glucose metabolism, it is also involved in metabolism of fructose and galactose.

Glucokinase, on the other hand, is specific for glucose. It has high Km (i.e., low affinity for glucose), high Vmax and unlike hexokinase, it is not inhibited by glucose-6-phosphate. As it has low affinity for glucose (high km), it comes into play only when intracellular glucose concentration is high. It is induced by feeding and insulin. Glucagon inhibits glucokinase.

Function of hexokinase is to provide glucose-6-phosphate at a constant rate, according the needs of cells, i.e., function of hexokinase is to provide constant glucose utilization by all tissues of body even when blood sugar is low. Function of glucokinase in the liver is to remove glucose from blood after a meal, providing glucose-6­phosphate in excess of requirement for glycolysis so that it can be used for glycogen synthesis and lipogenesis.

Phosphofructokinase I

Phosphofructokinase I is the major regulatory enzyme of glycolysis. It catalyzes the 3rd reaction of glycolysis, i.e., fructose-6-P Fructose 1,6 bis-P. This reaction is irreversible and is the “rate -limiting step” for glycolysis. It is also the “commeted step”, meaning that once fructose 1,6 bisphophate is formed it must go for the glycolytic pathway only. So, most important control point for glycolysis is through regulation of phosphofructokinase I.

Phosphofructokinase – I is allosterically activated by : Fructose-6-phosphate, fructose 2,6-bisphophate, AMP, ADP, K+ and phosphate. It is allosterically inhibited by : ATP, citrate, Ca+2, Mg+2, and low pH. Phosphofructokinase is an inducible enzyme that increases its synthesis in response to insulin and decreases in response to glucagon.

Fructose 2,6-bisphosphate (F-2,6-BP) is the most important allosteric modulator (activator) of phosphofructokinase-I. Fructose 2,6-bisphosphate is synthesized as a side product of glycolysis. A bifunctional enzyme named PFK-2/Fructose 2,6 bisphosphatase is responsible for regulating the level of fructose 2,6 bisphosphate in the liver. Phosphofuctokinase-2 (PFK-2) activity of this bifunctional enzyme is responsible for synthesis of F-2,6-BP from fructose-6-phosphate and fructose 2,6 bisphosphatase activity is responsible for hydrolysis of F-2,6-BP back to fructose-6-phosphate.

Q. 32

Which of the enzyme of glycolysis is used ingluconeogenesis ‑

A

Glucokinase

B

PFK

C

Pyruvate kinase

D

Phosphotriose isomerase

Q. 32

Which of the enzyme of glycolysis is used ingluconeogenesis ‑

A

Glucokinase

B

PFK

C

Pyruvate kinase

D

Phosphotriose isomerase

Ans.

D

Explanation:

Ans. is ‘d’ i.e., Phosphotriose isomerase

Enzyme in gluconeogenesis

Seven of the reactions of glycolysis are reversible and are used in the synthesis of glucose by gluconeogenesis. Thus, seven enzymes are common to both glycolysis and gluconeogenesis: (i) Phosphohexose isomerase; (ii) Aldolase; (iii) Phosphotriose isomerase; (iv) Glyceraldehyde 3-phosphate dehydrogenase; (v) Phosphoglycerate kinase; (vi) Phosphoglycerate mutase; (vii) Enolase.

Three of the reactions of glycolysis are irreversible and must be circumvented by four special reactions which are unique to gluconeogenesis and catalyzed by : (i) Pyruvate carboxylase, (ii) PEP carboxykinase, (iii) Fructose-1, 6- bisphosphatase, (iv) Glucose-6-phosphatase.

Q. 33

Which of the enzyme of glycolysis is a part ofgluconeogenesis ‑

A

Pyruvate kinase

B

PFK

C

Hexokinase

D

Phosphoglycerate kinase

Q. 33

Which of the enzyme of glycolysis is a part ofgluconeogenesis ‑

A

Pyruvate kinase

B

PFK

C

Hexokinase

D

Phosphoglycerate kinase

Ans.

D

Explanation:

Ans. is ‘d’ i.e., Phosphoglycerate kinase

Seven of the reactions of glycolysis are reversible and are used in the synthesis of glucose by gluconeogenesis. Thus, seven enzymes are common to both glycolysis and gluconeogenesis: (i) Phosphohexose isomerase; (ii) Aldolase; (iii) Phosphotriose isomerase, (iv) Glyceraldehyde 3-phosphate dehydrogenase; (v) Phosphoglycerate kinase; (vi) Phosphoglycerate mutase; (vii) Enolase.

Three reactions of glycolysis are irreversible which are circumvented in gluconeogenesis by four reactions. So, enzymes at these steps are different in glycolysis and gluconeogenesis.

Cancer cells derive nutrition from glycolysis as they have lack of 02 supply because of lack of capillary network. Glycolysis (anaerobic glycolysis) is the only metabolic pathway in the body which can provide energy by glucose metabolism in anerobic conditions.

Q. 35

Anaerobic glycolysis occurs in all places except

A

Muscles

B

RBCs

C

Brain

D

Kidney

Q. 35

Anaerobic glycolysis occurs in all places except

A

Muscles

B

RBCs

C

Brain

D

Kidney

Ans.

C

Explanation:

Ans. is ‘c’ i.e., Brain

There are two types of glycolysis : –

Aerobic glycolysis : – It occurs when oxygen is plentiful and the final product is pyruvate, i.e., final step is catalyzed by pyruvate kinase (see the cycle above). Which is later converted to acetyl CoA by oxidative decarboxylation. There is net gain of 7 ATPs. Acetyl CoA enters TCA cycle.

Anaerobic glycolysis : – It occurs in the absence of oxygen. The pyruvate is fermented (reduced) to lactate in single stage. The reoxidation of NADH (formed in the glyceraldehyde-3-phosphate dehydrogenase step) by respiratory chain is prevented as same NADH is utilized at lactate dehydrogenase step. So, there is no net production of NADH. Thus, there is net gain of 2 ATP only. Unlike pyruvate which is converted to acetyl CoA to enter into krebs cycle, lactate cannot be further utilized by further metabolic pathways. Thus, lactate can be regareded as dead end in glycolysis. Anaerobic glycolysis occurs in exercising skeletal muscle, RBCs, lens, some region of retina, renal medulla, testis and leucocytes.

Q. 36

Reducing equivalants produced in glycolysis are transported from cytosol to mitochondria by ‑

A

Carnitine

B

Creatine

C

Malate shuttle

D

Glutamate shuttle

Q. 36

Reducing equivalants produced in glycolysis are transported from cytosol to mitochondria by ‑

A

Carnitine

B

Creatine

C

Malate shuttle

D

Glutamate shuttle

Ans.

C

Explanation:

Ans. is ‘c’ i.e., Malate shuttle

Most of the NADH and FADH2, entering the mitochondrial electron transport chain arise from citric acid cycle and 13-oxidation of fatty acids, located in the mitochondria itself.

However, NADH is also produced in the cytosol during glycolysis.

To get oxidized, NADH has to be transported into the mitochondria as respiratory chain (ETC) is located inside the mitochondria.

Since, the inner mitochondrial membrane is not permeable to cytoplasmic NADH, there are special shuttle systems which carry reducing equivalents from cytosolic NADH (rather than NADH itself) into the mitochondria by an indirect route.

Two such shuttle systems that can lead to transport of reducing equivalent from the cytoplasm into mitochondria are : –

Malate shuttle (malate-aspartate shuttle system).

Glycerophosphate shuttle.

Q. 37

Inhibition of glycolysis by increased supply of 02 is called ‑

A

Crabtree effect

B

Pasteur effect

C

Lewis effect

D

None

Q. 37

Inhibition of glycolysis by increased supply of 02 is called ‑

A

Crabtree effect

B

Pasteur effect

C

Lewis effect

D

None

Ans.

B

Explanation:

Ans. is ‘b’ i.e., Pasteur effect

Pasteur effect

It has been observed that under anaerobic condition a tissue or microorganism utilizes more glucose than it does under aerobic conditions.

It reflects inhibition of glycolysis by oxygen and is called pasteure effect.

The Pasteur effect is due to inhibition of the enzyme phosphofructokinase because of inhibitory effect caused by citrate and ATP, the compounds produced in presence of oxygen due to operation of TCA cycle. Crabtree effect

This is opposite of Pasteur effect, which represents decreased respiration of cellular systems caused by high concentration of glucose.

When oxygen supply is kept constant and glucose concentration is increased, the oxygen consumption by cells falls, i.e., relative anaerobiosis is produced when glucose concentration is increased in constant supply of oxygen.

It is seen in cells that have a high rate of aerobic glycolysis.

In such cells the glycolytic sequence consumes much of the available Pi and NAD+, which limits their availability for oxidative phosphorylation.

As a result, rate of oxidative phosphorylation decreases, and oxygen consumption also shows a corresponding fall.

Tyrosine is a precursor of many important compounds such as catecholamines (epinephrine, norepinephrine ), dopamine), thyroxine, triiodothryonine, melanin.

Q. 3

Enzyme deficient in tyrosinemia type 1 ‑

A

Phenylalanine hydroxylase

B

Tyrosinase

C

Fumarylacetoacetate hydroxylase

D

Tyrosine transaminase

Q. 3

Enzyme deficient in tyrosinemia type 1 ‑

A

Phenylalanine hydroxylase

B

Tyrosinase

C

Fumarylacetoacetate hydroxylase

D

Tyrosine transaminase

Ans.

C

Explanation:

Tyrosinemia

It is a defect in metabolism of tyrosine. It may be of following types :-

Tyrosinemia type-I (tyrosinosis/hepatorenal syndrome) :- It is due to defect in fumarylacetoacetate hydroxylase deficiency. Patients with chronic tyrosinosis are prone to develop cirrhosis and hepatic carcinoma. There is cabbage like odor in acute tyrosinosis.